1. Field of the Invention
The present invention is in the field of ophthalmology, and more particularly concerns measuring macular pigment by imaging the macula with a plurality of wavelengths simultaneously.
2. Description of the Related Art
There are a number of circumstances that arise in ophthalmology in which it is necessary or desirable to measure macular pigment. Increased ingestion of lutein and zeaxanthine has been associated with increased risk of macular degeneration in some studies.3 (All bibliographic references are listed by number in Table I.) Supplements to increase the amounts of these pigments are a popular means to try to decrease the risk of macular degeneration. The absorption of these pigments appears to vary from individual to individual.4,5 Some studies suggest a correlation between serum levels of lutein and zeaxanthine and reduced risk, while others do not.6-8 However, the relationship between blood levels of these pigments and ultimate deposition in the macula is not known with certainty. In some circumstances there appears to be increased metabolism of macular pigments. Smoking, for example, is associated with decreased levels of macular pigment.9 Obesity is also associated with decreased pigment,10 perhaps because these pigments are fat soluble.
Having a method to measure macular pigment would help in evaluating and treating older patients at risk for macular degeneration. There are several ways to measure macular pigment. Heterochromatic flicker matching is a psychophysical test where the person has to adjust the brightness of colors so that they match. This is difficult for some patients to do, particularly as they get older. This test measures only one point in the macula, the one used to visualize the colors. The tester does not know what point is being measured. It is likely that the distribution of macular pigments in the macula is important, not just the amount at the one point being measured. Raman spectroscopy, another measurement method, uses inelastic scattering of the macular pigments to measure their presence. Raman spectroscopy measures one point in the eye and the exact location of this point is not known to the tester.
Additional methods used to measure the amount of macular pigment usually use more than one wavelength. Reflectance photography uses two wavelengths. The first wavelength is blue, in the region of maximal absorbance of the macular pigment, which is around 465 nm. The second wavelength chosen is to be somewhat longer, but out of the range of maximal absorption of the macular pigment, which declines to low levels at wavelengths longer than 530 nm. The ratio of the optical absorption at the two test wavelengths can be used to calculate the optical density.
Autofluorescence photographic approaches also can use two wavelengths to estimate the amount of macular pigment present. In this method two wavelengths are used to stimulate autofluorescence, one blue and another that is usually in the green portion of the spectrum. The blue light would be blocked by the macular pigment while the green light would not. The ratio of the induced autofluorescence would be indicative of the amount of macular pigment.
There are advantages to both the reflectance photography and autofluorescence methods. The reflectance method does not rely on the unproven assumption that the difference in the amount of fluorescence caused by the two wavelengths is only due to the presence of blue light absorbing pigments. Reflectance methods may, however, contain artifactual errors in that the surface of the retina may reflect light in inverse proportion to the wavelength used. This would increase the amount of blue light reflected, causing an underestimation of the amount of macular pigment present. An advantage of both methods is that a map of the amount of macular pigment is produced, not just a point estimate. Since macular degeneration involves the entire macula, knowledge of the topographical distribution of macular pigment would likely be more useful. On the other hand, these methods have a common disadvantage. Because two wavelengths are used, two different pictures need to be taken of the fundus. Even if these pictures are taken in close proximity to each other there is invariably movement of the eye and camera. This movement causes slight shifts in the field of view, magnification, and lighting of the fundus. It is possible to correct for these changes with the use of digital image processing software, but the corrections necessary take time, potentially introduce artifacts, and require specialized software.
TABLE 1References1Bhosale P, Bernstein PS. Synergistic effects ofzeaxanthin and its binding protein in the preventionof lipid membrane oxidation. Biochim Biophys Acta.2005; 1740: 116-21.2Davies NP, Morland AB. Macular pigments: theircharacteristics and putative role. Prog Retin EyeRes. 2004; 23: 533-59.3Seddon JM, Ajani AU, Sperduto RD, et al. Dietarycarotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA 1994; 272: 1413-20.4Curran-Celentano J, Hammond BR Jr, Ciulla TA, et al.Relation between dietary intake, serum concentrations,and retinal concentrations of lutein and zeaxanthinin adults in a Midwest population. Am J Clin Nutr.2001; 74: 796-802.5Hammond Jr., BR, Fuld, K and Curran-Celentano, J,1995. Macular pigment density in monozygotic twins.Invest. Ophthalmol. Vis. Sci. 36, pp. 2531-2541.6Mares-Perlman JA, Brady WE, Klein R, Klein BE, BowenP, Stacewicz-Sapuntzakis M, et al. Serum antioxidantsand age-related macular degeneration in apopulation-based case control study. ArchOphthalmol. 1995; 113: 1518-1523.7Mares-Perlman JA, Fisher AI, Klein R, Palta M, BlockG, Millen AE, el al. Lutein and zeaxanthin in thediet and serum and their relation to age-relatedmaculopathy in the third national health and nutritionexamination survey. Am J Epidemiol 2001; 153: 424-32.8Dasch B, Fuhs A, Schmidt J, et al. Serum levels ofmacular carotenoids in relation to age-relatedmaculopathy: the Muenster Aging and Retina Study (MARS).Graefes Arch Clin Exp Ophthalmol. 2005; 243: 1028-35.9Hammond Jr., BR, Wooten, BR and Snodderly, DM, 1996.Cigarette smoking and retinal carotenoids:implications for age-related macular degeneration.Vision Res. 36, pp. 3003-3009.10Hammond Jr., BR Ciulla, T.A. and Snodderly, DM, 2002.Macular pigment density is reduced in obese subjects.Invest. Ophthalmol. Vis. Sci. 43, pp. 47-50.